Time for Routine Helicobacter pylori Screening in Coronary Artery Disease?

Antiplatelet therapy in coronary artery disease involves a tradeoff between the risk of recurrent cardiovascular events and spontaneous bleeding, commonly from the upper gastrointestinal tract. Gastrointestinal injury diagnosed by capsule endoscopy occurs in 94.3% of patients on single antiplatelet therapy during the first year after percutaneous coronary intervention, rising to 99.2% in those on dual antiplatelet therapy,1 illustrating the extent of the clinical dilemma. Severe upper gastrointestinal bleeding (UGIB) requiring hospitalization is relatively common, with a 1.5% cumulative incidence in the year after myocardial infarction (MI), and associated with a substantially increased risk of death (hazard ratio, 2.86) and recurrent cardiovascular events (hazard ratio for MI or stroke, 1.17 and 1.80, respectively).2 Recommended bleeding avoidance strategies encompass prophylactic use of proton pump inhibitors as well as individualization of dual antiplatelet therapy in terms of shorter duration, de-escalation to less potent therapies, and single treatment with either aspirin alone or aspirin-free strategies.2,3

A ntiplatelet therapy in coronary artery disease involves a tradeoff between the risk of recurrent cardiovascular events and spontaneous bleeding, commonly from the upper gastrointestinal tract. Gastrointestinal injury diagnosed by capsule endoscopy occurs in 94.3% of patients on single antiplatelet therapy during the first year after percutaneous coronary intervention, rising to 99.2% in those on dual antiplatelet therapy, 1 illustrating the extent of the clinical dilemma. Severe upper gastrointestinal bleeding (UGIB) requiring hospitalization is relatively common, with a 1.5% cumulative incidence in the year after myocardial infarction (MI), and associated with a substantially increased risk of death (hazard ratio, 2.86) and recurrent cardiovascular events (hazard ratio for MI or stroke, 1.17 and 1.80, respectively). 2 Recommended bleeding avoidance strategies encompass prophylactic use of proton pump inhibitors as well as individualization of dual antiplatelet therapy in terms of shorter duration, de-escalation to less potent therapies, and single treatment with either aspirin alone or aspirin-free strategies. 2,3 H PYLORI AS A MODIFIABLE RISK FACTOR TO PREVENT UPPER GI BLEEDING AFTER MI Risk factors for UGIB during antiplatelet treatment include high age, female sex, kidney disease, anemia, and chronic bacterial infection caused by Helicobacter pylori. 2,4 Concomitant H pylori infection increases the risk of upper GI bleeding, from 1.8-fold with low-dose aspirin up to 7.4-fold with dual antiplatelet therapy. 4 In addition to endoscopic sampling, H pylori infection can be detected noninvasively with similar high accuracy using fecal H pylori antigen test, serology, or urea breath test (sensitivity/specificity ≈90%), 3 allowing for broad screening. 4 H pylori eradication treatment is recommended using a combination of different antibiotics, depending on individual and regional resistance profiles, and proton pump inhibitors, aiming for successful eradication rates >90% with first-line therapy, and thereby effectively healing ulcers. 4 Successful H pylori eradication may reduce the risk of UGIB complications and allow uninterrupted antiplatelet therapy, both potentially contributing to beneficial effects on subsequent cardiovascular outcomes. 2,4 In addition, H pylori infection may promote development of atherothrombosis through (1) chronic inflammation and direct injury of the vascular wall leading to progression or rupture of atherosclerotic plaque and (2) a systemic inflammatory response in reaction to colonization of the gastric mucosa. These inflammatory processes can induce prothrombotic changes in the blood both related to plasma (ie, hyperfibrinogenemia, altered blood coagulation) and platelet-dependent (ie, induced platelet count, activation, and aggregation [eg, by lipid peroxidation]) homeostasis (summarized in reference 3 ), thus contributing to the development of acute coronary syndrome.
Because of a lack of data from randomized clinical trials, H pylori screening and eradication is recommended by expert opinion in gastroenterology guidelines, but hitherto largely disregarded in cardiology guidelines. 4

Hofmann and Bäck
H pylori Screening in CAD?

ROUTINE H PYLORI SCREENING AND ERADICATION MAY REDUCE PEPTIC ULCER BLEEDING, BUT QUESTIONS REMAIN
H pylori screening results recently were presented from the randomized, double-blind, placebo-controlled HEAT (Helicobacter Eradication Aspirin Trial), conducted at 1208 primary care facilities in the United Kingdom. The study reported an active H pylori infection detected by urea breath test in 17.8% of 30 166 unselected individuals receiving ≤325 mg daily aspirin. 5 Together with the previously reported 20% H pylori prevalence in contemporary patients with myocardial infarction in Sweden, 4 these findings support H pylori as a widespread risk factor for bleeding complications from cardiovascular prevention measures. The HEAT investigators demonstrate for the first time a significant reduction in UGIB by routine H pylori screening and eradication. However, several limitations merit consideration. First, the trial was terminated early because of a lower-than-expected event rate and thus was underpowered for the primary end point. Second, the analyses may not sufficiently account for competing risks of death attributable to conditions other than bleeding. Third, because of the pragmatic design of the trial, the use of gastroprotective therapies to prevent gastric complications was uncontrolled, which may have biased the results. Fourth, the observed treatment effect of a reduction in UGIB was only transient, and the benefit was lost beyond 2.5 years of follow-up. 5 In particular, the loss of bleeding protection over time remains to be understood. The authors cite enhanced acid secretion or reduced release of protective prostaglandins after H pylori eradication as possible explanations. 5 Reinfection rates with H pylori, another rare (1% to 3% in adult age) but possible explanation, were not monitored. Moreover, because of the uncontrolled use of gastroprotective treatment, the results do not allow answers to the clinically important question of whether guideline-recommended use of proton pump inhibitors may have mitigated the excess bleeding risk enough to reduce its relevance or the impetus of H pylori screening and eradication.

ONGOING STUDY IN PATIENTS WITH ACUTE MI
Are the results from HEAT enough to strengthen current guidelines? Considering the limitations mentioned, controversy remains regarding the optimal target group and timing of a routine H pylori test-and-treat strategy. Focusing on patients with strong indication for potent antiplatelet therapy but also a higher risk of UGIB may

SUMMARY
The encouraging but inconclusive results from HEAT in unselected low-dose aspirin users underline the need for determining the usefulness of routine H pylori screening, as well as optimal timing of H pylori eradication, in patients with high-risk coronary artery disease on more potent antithrombotic medication for optimized cardiovascular prevention.